Chou Chia-Lin, Chen Tzu-Ju, Li Wan-Shan, Lee Sung-Wei, Yang Ching-Chieh, Tian Yu-Feng, Lin Cheng-Yi, He Hong-Lin, Wu Hung-Chang, Shiue Yow-Ling, Li Chien-Feng, Kuo Yu-Hsuan
Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan.
Division of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
Onco Targets Ther. 2022 Oct 11;15:1171-1181. doi: 10.2147/OTT.S378666. eCollection 2022.
For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT.
We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival.
Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004).
UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.
对于局部晚期直肠癌,新辅助同步放化疗(CCRT)可使肿瘤降期,并使根治性直肠切除术成为可能。然而,我们缺乏一种基因生物标志物来预测癌症预后或治疗反应。我们研究了接受CCRT的直肠癌患者中泛素D(UBD)表达与临床结局之间的关联。
我们分析了与蛋白质修饰过程相关的基因(GO:0036211),并确定UBD基因是与CCRT耐药相关的前7个差异表达基因中最相关的基因。我们收集了172例接受CCRT后行根治性直肠切除术的直肠癌患者的组织标本。我们研究了UBD表达与患者特征、病理结果以及患者生存之间的关系,如无转移生存期(MeFS)和疾病特异性生存期。
UBD表达上调与CCRT前较低的肿瘤T分期(P = 0.009)、CCRT后较低的肿瘤T分期(P < 0.001)、CCRT后较低的淋巴结分期(P < 0.001)、较少的血管侵犯(P = 0.015)以及较好的肿瘤退缩(P < 0.001)相关。单因素分析显示,高UBD表达与较好的无病生存期(DFS)(P < 0.0001)、无局部复发生存期(LRFS)(P < 0.0001)和MeFS(P < 0.0001)相关。此外,多因素分析表明,高UBD表达与较好的DFS(P < 0.001)、LRFS(P = 0.01)和MeFS(P = 0.004)相关。
UBD上调与接受CCRT的直肠癌患者更好的临床预后、良好的病理特征和良好的治疗反应相关。这些结果表明UBD是直肠癌的一种生物标志物。